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p53 involvement in clonal hematopoiesis of indeterminate potential

Chen, Sisia; Liu, Yana,b

Current Opinion in Hematology: July 2019 - Volume 26 - Issue 4 - p 235–240
doi: 10.1097/MOH.0000000000000509
HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano
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Purpose of review Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and occurs when a single mutant hematopoietic stem cell (HSC) contributes to a significant clonal proportion of mature blood lineages. Somatic mutations in the TP53 gene, which encodes the tumor suppressor protein p53, rank in the top five among genes that were mutated in CHIP. This review focuses on mechanisms by which mutant p53 promotes CHIP progression and drives the pathogenesis of hematological malignancies, including myelodysplastic syndromes, and acute myeloid leukemia.

Recent findings TP53 was frequently mutated in individuals with CHIP. Although clinical studies suggest that expansion of HSCs with TP53 mutations predisposes the elderly to hematological neoplasms, there is a significant gap in knowledge regarding the mechanisms by which TP53 mutations promote HSC expansion. Recent findings suggest that several cellular stressors, including hematopoietic transplantation, genotoxic stress, and inflammation, promote the expansion of HSCs with TP53 mutations. Further, TP53 mutations identified in CHIP cooperate with genetic and/or epigenetic changes in leukemogenesis.

Summary TP53 mutations identified in CHIP are associated with increased risks of de novo and therapy-related hematological neoplasms. Thus, targeting mutant p53 and related pathways holds great potential in preventing CHIP progression and treating hematological malignancies.

aDepartment of Biochemistry and Molecular Biology

bDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University, Indianapolis, Indiana, USA

Correspondence to Yan Liu, PhD, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University, Indianapolis, IN 46202, USA. Tel: +1 317 278 0333; fax: +1 317 274 8679; e-mail: liu219@iu.edu

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